Your Digest for Wednesday, Jan 31, 2024 09:59 AM

[!TIP] mnemonic: 'flozins' are SGLT-2 inhibitors
Glucose 'flowz in' the PCT

General properties of hypoglycaemic agents

Protective effects of hypoglycemic agents

Source

Evidence on protective effects of hypoglycemic agents

Source

Indications for selecting a hypoglycemic agent

| Agent | Class | Mechanism | Side effects | Other stuff | Expected effect |
| ------------------------------------------------ | -------------------------------- | --------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------- |
| Metformin | Biguanide | Insulin sensitiztion Reduce hepatic gluconeogenesis. | GI side effects Lactic acidosis (risk in renal/liver/heart failure – contrindications) No weight gain May reduce apetite, STOP when eGFR < 30 | Reduced GI B12 absorption The usual first line agent, can be combined with other | Lower FBS by about 50 mg/dL Lowers HbA1C by about 1% |
| Pioglitazone is the only one | Thiazolidinediones (glitazones) | Increases insulin sensitivity by binding nuclear receptors and altering gene expression may increase glucose consumption in muscle cells | no hypoglycaemia Commonly weight gain Fluid retention → precipitates Heart failure | May specifically benefit NAFLD | take up to 3 months to reach maximal effect. |
| Gliclazide Glimipiride Glibenclamide Tolbutamide | Sulphonylureas | Promotes depolarization of beta cell → stimulates insulin secretion (by binding ATP dependent k+ channel) | Weight gain! Hypoglycaemia | Effect will wear off with age as beta cell mass declines Risk of hypoglycaemia increases with age and intercurrent infection and duration of drug action Gliclazide / Glipizide / tolbutamide → Short acting Glimiperide → ? long acting but lower hypo risk Glyburide(= Glibenclamide) – long acting | Similar to metformin Weight gain of 1-4 Kg |
| Repaglinide | Meglitinides ("slp.ureas lite") | Post prandial insulin releasers (binds ATP dependent k+ channel like sulfonylureas) but act only for 3 hrs. So effective only in post prandial period when taken with meals | Hypoglycaemia Weight gain (but less than s.ureas) | Taken about 30 minutes before meals. | Less effective than other drugs. Role in DM Mx is not clear. Can be used with metformin is C/I or when patient only has post prandial hyperglycaemia |
| Sitagliptin Linigliptin | DPP-4 inhibitors (gliptins) | Inhibit GLP-1 breakdown (restore physiologic GLP levels) → promotion of insulin secretion GLP1 receptors are also found in the cardiovascular system | Good S/E profile. | Used as second line drug, in early DM when insulin secretion is still preserved. Combined with metformin / sulfonylurea | Modest effect but used because of low S/E profile. |
| Empagliflozin Dapagliflozin Canagliflozin | SGLT inhibitors | Inhibit the coupled reabsorption of sodium and glucose from the proximal tubules (+ other renal effects) | Dehydration Genital candidiasis (but not bacterial UTI),Can precipitate DKA (increase production of ketones) | Wonder drug! Decreases weight Improve renal dysfuntion – renoprotective Reduce atherosclerotic events! Reduce risk of heart failure | ?More potent glucose lowering than metformin(values given in K&C). Weight loss of 2-4 Kg over 1 year |
| GLP - Agonists - See Below | | | | | |
| | | | | | |

- *GI symptoms*

extrapulmonary manifestations:

• liver enzyme elevation
• myocardial: conduction abnormalities (heart block)
• dermatologic (e. Multiforme, e nodosum)
• renal and cns are rare.
• Source

Diagnosis: fastidious organism, use PCR

• Protozoanf
• Obligate human parasite (Humans are only known host)
• Ingestion of sporulated oocyst from fruits / vegetables / water -> infection -> infection of GI mucosa
• Low grade fever with anorexia, nausea, flatus, diarrhoea (symptoms can be chronic)
• "symptomatic infections typically manifest as watery diarrhea of varying severity. Other manifestations include complications of dysentery, further abdominal symptoms, and sometimes non-specific systemic symptoms"
• Direct faeco oral transmission is not possible as defecated unsporulated oocyst must mature for days / weeks in the environment.
• Diagnosis: wet mount stool microscopy or PCR.
• Treatment: trimethoprim sulfamethoxazole.
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[!INFO] Ergot Vs. Non Ergot antiparkinson medications: Fibrosis Vs Non fibrotic

• Ergot derived antiparkinson medications: Pergolide, Lisuride, Bromocriptine and cabergoline
• Non ergot derived antiparkinson medication are the newer class: Ropinirole
  • Others are pramipexole, ropinirole, rotigotine and apomorphine
• Ergot is a fungus which secretes psychoactive substances.
• Ergot derived antiparkinson mediations have increased risk of fibrotic reactions (pericardial, pleural, retroperitoneal) due to stimulation of serotonin receptors.

[!TIP] Mnemonic:

Ergot derived	NON ergot
Fungal PeLiCan B	PramOnRottinRope
Pergolide, Lisuride, Cabergoline, Bromocriptine	pramipexole, ropinirole, rotigotine

5. Humans can get infected by

[!INFO] See [[#Comparison of amoebiasis and giardiasis]] below

• Infection occurs by ingestion of mature cysts from water or foods with faecal contamination.

Comparison of amoebiasis and giardiasis

• With toxic doses of PCM, glutathione which conjugates harmful NAPQI becomes depleted, leaving NAPQI (N-acteyl P benzoquinone imine) to inflict liver damage.
• NAPQI binds irreversibly to mitochondrial proteins.
  
  • Signs of severe hepatotoxicity include
    • plasma ALT and AST levels that often exceed 10,000 IU/L
    • prolongation of the PT/INR,
    • hypoglycemia, lactic acidosis,
    • and a total bilirubin concentration above 4.0 mg/dL or 68 micromol/L, (primarily indirect)
    • fulminant hepatic failure (hepatic failure is differentiated from liver injury by the onset of impaired synthetic function and/or encephalopathy)
      NAC infusion is continued according to the protocol. Some recommend that infusion is stopped based on time.
      Treatment can be stopped when all of the following are met.

4. Patient is clinically well.